Olanzapine has frequently been reported to induce substantial weight gain, which is associated with an increased prevalence of dyslipidemia and type 2 diabetes. Several reports have described that olanzapine orally disintegrating tablets (ODT) induce less weight gain than oral standard tablets (OST) do, although both forms have equal bioavailability. We tried to clarify whether or not body weight change differed between olanzapine ODT and OST treatments in olanzapine-naïve schizophrenia patients. An open-label, 12-month, multicenter, randomized, flexible-dose study was conducted for direct comparison of the effects of OST (mean dosage, 15.7 mg; N = 57) and ODT (mean dosage, 15.2 mg; N = 61) on body weight and metabolic measures such as blood glucose, hemoglobinA1c, total cholesterol and HDL-cholesterol, and triglycerides in olanzapine-naïve patients with schizophrenia. Outcome measures included Positive and Negative Syndrome Scale (PANSS), Global Assessment of Function (GAF), The World Health Organization Quality of Life 26 (WHO-QOL26), Drug Attitude Inventory (DAI)-10, and tolerability assessed by the UKU side-effect rating scale. This study was conducted between June 2007 and April 2010. No significant difference was found in the weight gain between the two forms of olanzapine. No significant difference was found between the two groups in any metabolic measure, efficacy, tolerability, WHO-QOL26, or DAI-10 score. Previous reports describing that olanzapine ODT induced less weight gain than OST were not supported by results of this randomized study.